In no other scientific field does the adage "form follows function"
hold more true than in biology, especially the biology of living cells,
which is why much of our knowledge of cell proteins starts with imaging.
Throughout the 1990s, the best images of proteins in cells came from confocal
microscopy, a technique whereby thousands of pinpoints of laser light
are used to produce highly-focused images that are unmatched for contrast
and clarity by conventional visible light microscopy.

Used in combination with fluorescent labeling, in which fluorescently-tagged
antibodies bind to specific proteins for identification, confocal microscopy
has lit the way for many of the recent advances in cell biology. However,
the information obtained will always be limited by the technique's relatively
low spatial resolution  about 200 nanometers (billionths of a meter).
Electron microscopy provides outstanding resolution -- down to one-tenth
of a nanometer -- but cells must be sectioned off into tissue-thin slices
for imaging because even highly-energized electrons are poor penetrators.
Also, the cell slices must be dehydrated and embedded in plastic as electron
microscopy can only be done in a vacuum. This involves chemicals that
can damage or destroy proteins, or interfere with the ability of antibodies
to bind to the proteins.

The
exterior and interior structures of cells are reconstructed by computer
visualization from dozens of separate images taken with an x-ray microscope.
Colors are assigned to different structures on the basis of x-ray
absorption. These 3-D images can be viewed from any angle, or as a
motion picture.

What scientists have needed is an alternative that can provide higher
resolution information on internal cell structures cells without requiring
elaborate specimen preparation and cell dehydration. X-ray microscopy
using low energy or "soft" x-rays fits the bill. Cell biologist
Carolyn Larabell and her research team are using a soft x-ray microscope
at Berkeley Lab's Advanced Light Source to image intact hydrated cells
at a resolution between 40 and 50 nanometers. With their technique, they
can obtain high-contrast images of the internal structures of these cells
without even having to stain them.

"We've demonstrated a practical technique that
gives cell biologists a whole new way of looking at their samples,"
Larabell says. "Soft x-ray microscopy is now ready to make a major
contribution to the understanding of cell function and structure."